The volatile anesthetics halothane (H) and enflurange (E) depress the slow inward calcium currents in myocardial tissue by an unknown mechanism. This effect may be in part responsible for the myocardial contractile depression by these drugs, since influx of extracellular calcium may trigger intracellular calcium release and also directly supply calcium for myofibrillar activation. The depression f slow action potentials (mediated by slow currents) may also be responsible for the depressed atrioventricular conduction seen with halothane and enfluane. These volatile anesthetic effects are similar to those obsered for the specific calcium chsnnel blockers (verapamil, nifendipine, diltiazem) upon the hear; that is, inhibition of slow inward current and slow action potentials, decreased atrioventricular conduction, and depressed myocardial contractility. Wide application of the calcium channel blockers is anticipated in treatment of angina (because of their vasodilating actions) and arrhythmias. Since the volatile anesthetics and calcium channel blockers have similar electrophysiologic effects, simultaneous administration may lead to marked depressio of slow inward current and consequent depresson of cardiac contractility and conduction. This study will explore the effect of volatile anesthetics (H, E, and also isoflurane) on the ionic currents in voltage clamped guinea pig myocardium. The voltage clamp technique permits measurement of changes in specific transmembrane curent flows. Alterations in the kinetics and/or quantity of slow inward (calcium) and late outward (potassium) currents will define specific mechanisms of action and identify differential effects among these anesthetics. Anesthetic effects on the voltage dependence of contractile activation will also be determined. Subsequently, the interaction of each anesthetic with each calcium channel glocker (verapamil, nifedipine, or diltiazem; nine possible comibnations exist) will be studied on fast action potentials and slow action potentials with their accompanying contractions. Voltage clamp analysis of the combined effects will also be performed where more complex interactions between the anesthetic and calcijm antagonist are suggested by action potential experiments. Basic electrophysiologic study can predict potentially severe interactions resulting clinically in heart failure or total heart block.